Abstract: Disclosed are novel means of enhancing efficacy of pancreatic islet transplantation through administration of regenerative T cells concurrently with modification of the local microenvironment to provide a tolerogenic and angiogenic milieu. In one embodiment, the liver microenvironment is prepared for receipt of pancreatic islets by administration of tolerogenic cells antigen presenting cells, subsequently followed by administration of T cells and/or T regulatory cells conditioned by regenerative cells, and finally pancreatic islets are administered. In other embodiments devices are provided which allow for concurrent administration of pancreatic islets together with T cells and/or T regulatory cells that have been conditioned with regenerative cells. In another embodiment, the administration of T cells and/or T regulatory cells conditioned by regenerative cells is after administration of therapeutic pancreatic islets.

Abstract: Disclosed are means of treatment for age related or premature reproductive failure through concurrent administration of regenerative cells together with adjuvants capable of enhancing activity of said regenerative cells. In one embodiment, the invention provides administration of autologous bone marrow mononuclear cells in the endometrium and ovarian tissue. Administration of said type of regenerative cells is combined with anti-oxidants and/or regenerative adjuvants capable of reducing inflammation and/or fibrosis, as well as providing a suitable environment for optimal regenerative function of stem cells.

Abstract: Disclosed are prophylactic and therapeutic approaches to Orthopox viral infections. In one embodiment the invention teaches utilization of regenerative cell conditioned media as a prophylactic/therapeutic agent. Synergies with antivirals and immunotherapies are further described. In one specific embodiment, mesenchymal stem cells are activated in vitro with trigger agents activating Toll-Like Receptors (TLRs), NOD-Like Receptors (NLRs), and RIG-I-Like Receptors (RLRs) and conditioned media is isolated and utilized as a therapeutic. Quantification of activity is performed by assessment of antiviral activity and/or ability to stimulate NK mediated cytolysis. Additionally, means of treating Orthopox viral infections (Smallpox, Monkeypox, etc.) by direct administration of stem cells and/or products thereof such as exosomes are disclosed.

Abstract: Disclosed are means, methods and compositions of matter useful for prevention of space flight associated bone density loss. In one embodiment, the invention provides cellular populations capable of suppressing osteoclast function and/or stimulating osteoblast activity. The use of mesenchymal stem cell populations alone, or more preferably, selected by expression of CD56 protein are disclosed. Cells may be administered systemically, or locally through the use of various matrices disclosed in this invention.

Abstract: Disclosed are means, methods and compositions of matter for prevention of hair loss and/or regeneration of hair follicles utilizing stem cell-based approaches and synergies with stimulating and/or hormone modulating agents. In one embodiment the invention discloses specific platelet rich plasma (PRP) combinations alone or with bone marrow stem cells to augment hair restoration and stimulate expansion of hair follicle associated T regulatory cell.

Abstract: Methods and compositions are provided to treat limb ischemia such as Beurger's Disease through the use of bone marrow stem cells that are administered prior to, concurrently with, and subsequently to administration of agents that modify the microenvironment of the ischemic limb(s). In one embodiment, said agents are antioxidants, more specifically antioxidants capable of diffusing across ischemic areas and preserving regenerative activity of administered stem cells. In another embodiment, the invention provides hormonal modifications to overcome deficiencies associated with ischemia predisposing pathologies.

Abstract: Disclosed are methods, means, and compositions of matter useful for enhancing regenerative activity of bone marrow mononuclear cells/aspirate by coadministration with oxytocin. In one embodiment the invention teaches the treatment of peripheral artery disease by intramuscular administration of oxytoxin and bone marrow mononuclear cells/aspirate in proximity. The invention provides therapeutic doses, kits, and adjuvants useful in enhancing regenerative activity of bone marrow mononuclear cells/aspirate.

Abstract: Treatment of rheumatoid arthritis has been revolutionized by the introduction of TNF-alpha blockers, which represent a 40 billion dollar annual market. Unfortunately, a significant proportion of patients fail to respond to these treatments. The current invention provides the use of stem cell conditioned T cells to overcome resistance to TNF-alpha blockers by concurrently providing a source of immune modulatory and regenerative cells that synergize with TNF-alpha blockers.

Abstract: The invention provides means, methods and some compositions of matter useful to treat ovarian failure. In one embodiment progenitor cells possessing ability to differentiate along the monocytic and granulocyte linages are utilized as a source of cytokines for stimulation of ovarian repair/regeneration. Generation of said cells, such as classically termed myeloid derived suppressor cells is performed from sources including cord blood, bone marrow, mobilized peripheral blood and pluripotent stem cells. The invention further provides means of suppressing fibrosis and ongoing inflammation associated with ovarian dysfunction.

Abstract: Disclosed are novel cellular compositions of matter and treatment means for generation of universal donor regenerative T cells by exposure to mesenchymal stem cells or supernatant derived thereof. In one embodiment, regenerative T cells are created by differentiation of pluripotent stem cells in the presence of supernatant generated from activated mesenchymal stem cell population. The invention provides for creation of T cells which are capable of endowing regenerative activity, and/or anti-inflammatory, and/or angiogenic activity.

Abstract: Disclosed are means, methods and compositions of matter useful for generation of conditioned media from mesenchymal stem cells (MSC). In one embodiment MSC are extracted, dedifferentiated into inducible pluripotent stem cells (iPSC) and said iPSC are differentiated into the MSC lineage. The differentiated MSC are utilized as producers of conditioned media for therapeutic purposes. In one embodiment MSC are subjected to one or more stressors, after which conditioned media is extracted and in some cases concentrated. Said conditioned media can be utilized as a therapeutic agent or can be used in the generation of immune modulatory cells.

Abstract: Disclosed are means, methods and compositions of matter useful for generation of conditioned media from endothelial progenitor cells (EPC). In one embodiment, EPC are extracted, dedifferentiated into inducible pluripotent stem cells (iPSC) and said iPSC are differentiated into the EPC lineage. The differentiated EPC are utilized as producers of conditioned media for therapeutic purposes. In one embodiment EPC are subjected to one or more stressors, after which conditioned media is extracted and in some cases concentrated. Said conditioned media can be utilized as a therapeutic agent or can be used in the generation of immune modulatory cells.

Abstract: Disclosed are methods, compositions of matter and protocols useful for restoring/enhancing endometrial function by administration of regenerative cells. In one embodiment cells capable of decreasing fibrosis, stimulation of angiogenesis, and augmenting hormone responsiveness are administered systemically or locally. In some embodiments cells utilized are autologous or allogeneic mesenchymal stem cells.

Abstract: Disclosed are methods, compositions of matter and protocols useful for restoring/enhancing endometrial function by use of gene therapy. In one embodiment genes associated with endometrial preservation and/or regeneration are inserted into the endometrium and/or accessory tissues. Suppression of fibrosis, inflammation and stimulation of regeneration is accomplished by the practice of the current invention.

Abstract: Disclosed are novel means of generating cells uniquely suited for treatment of ovarian failure. In one embodiment regenerative cells are pretreated with growth factor-comprising composition(s), wherein the growth factor(s) may be cytokines, peptides, and/or proteins. In another embodiment regenerative cells are cultured with primed plasma extracts. In another embodiment, regenerative cells are cultured under hypoxic conditions together with cytokines prior to administration to an individual. Regenerative cells useful for the current invention including mesenchymal and hematopoietic stem cells, as well as various growth factor producing cells.

Abstract: Disclosed are compositions of matter, protocols, and procedures useful for generation of mesenchymal stem cells capable of withstanding the microenvironment of degenerating ovaries. In one embodiment mesenchymal stem cells are pre-treated under conditions capable of upregulating cytoprotective responses and genes, such as HIF-1 alpha and hemoxygenase. In other embodiments mesenchymal stem cells are temporarily pulsed with hypoxia and/or acidity in order to prime them for the harsh environment of degenerating ovarian tissue. Through this approach increased viability of mesenchymal stem cell subsequent to intra-ovarian administration is achieved.

Abstract: Described are protocols, compositions of matter and therapeutic means useful for treatment of ovarian failure caused by oncology treatments. The utilization of natural killer cells allows for dual activity of tissue regeneration in the ovary, while concurrently inhibiting possibility of oncology relapse. In embodiments NK cells are injected as an adjuvant to stem cell and/or regenerative cell therapy to not only enhance therapeutic effect but also to reduce probability of tumor relapse.

Abstract: Disclosed are methods, protocols and compositions of matter using for treatment of ovarian failure through administration of cells expressing FoxP3 as a monotherapy or as a facilitator to enhance therapeutic efficacy of cells and/or cytokines. In one embodiment FoxP3 expressing cells are concentrated from allogeneic umbilical cord blood, activated ex vivo with anti-CD3 and anti-CD28 antibodies and administered into the ovary alone or with regenerative cells such as stem cells. In one embodiment stem cells administered are of the CD105 expressing lineage.

Abstract: Disclosed are compositions of matter, protocols and procedures useful for preventing/treatment ovarian failure. In one embodiment cytokines promoting anti-inflammatory/regenerative activity are administered systemically, or locally in order to preventing ovarian degeneration/fibrosis. In one embodiment low dose interleukin-2 is administered either alone or with adjuvant cytokines to induce an increase in FoxP3 expressing CD4 cells. In some embodiments in vivo generation of FoxP3 expressing CD4 cells is associated with stimulation of intra-ovarian angiogenesis and prevention of fibrosis.

Abstract: Disclosed are means and methods useful in selecting osteoarthritis patients most likely to respond to regenerative medicine therapy. One means of practicing the invention is to determine quantity and quality of inflammatory exosomes generated from the tissue adjacent to the injured cartilage. In another embodiment the invention provides detection of exosomes produced by inflammatory processes local or systemic to the body. In some embodiments therapies are tailored to the extent of inflammatory exosomes.